JP6973779B2 - Composition for detecting air leaks during lung surgery - Google Patents

Description

The present invention relates to a composition for detecting air leaks during lung surgery.

After surgical lung resection, it is important to check for air leaks from the remaining lungs.

At present, the thoracic cavity is filled with physiological saline, and air is sent to the operated lung to pressurize and inflate, and the location of air leakage is visually confirmed from outside the thoracic cavity. On the other hand, in endoscopic surgery, which is currently the mainstream of lung resection, the thoracic cavity is operated by observing the inside with a scope inserted from outside the body into the working space in the thoracic cavity obtained by collapsing the lung. When the inside is filled with physiological saline and the lungs are pressurized, the working space disappears and it becomes difficult to observe the lung surface. However, at present, the presence or absence of an air leak or the identification of an air leak location has not been performed by any method other than this method.

Therefore, there are cases where the existence of air leaks can be detected only after the wound is closed and drainage is performed. In some cases, surgery is required.

As a result, there is a need to develop a more reliable method for identifying air leaks.

Biosurfactants, which are surfactants produced by microorganisms, show the same performance as surfactants obtained by chemical synthesis, and because they are highly biodegradable and low in toxicity, they are safe and have a low environmental load. It is an activator. Among them, sophorose lipid, which is a natural glycolipid produced by fermentation with yeast using vegetable oil (palm oil) and sugar as raw materials, consists of sugar (sophorose) and fatty acid (mainly oleic acid) and is relatively inexpensive. It is produced from raw materials and can be mass-produced.

Regarding sophorose lipid, a fermentation production method using Candida yeast to produce sophorose lipid in high yield and high yield (Patent Document 1), liquid and solid components from the culture termination liquid without using an organic solvent. (Patent Document 2) and the like have been reported as a method for obtaining a high-concentration solvent lipid by removing the yeast.

Japanese Unexamined Patent Publication No. 2002-45195 Japanese Unexamined Patent Publication No. 2003-9896

An object of the present invention is to provide a composition for detecting an air leak during lung surgery, which can more reliably confirm the presence or absence of an air leak and identify an air leak location in endoscopic surgery.

As a result of diligent research to achieve the above object, the present inventor pressurizes and inflates the lung with a surfactant applied to the surface of the lung, and after a while, causes the lung to collapse again and scopes the inside of the thoracic cavity. We obtained the finding that it is possible to confirm the presence or absence of air leaks and identify the location of air leaks by observing and searching for foaming spots.

The present invention has been completed by further studying based on these findings, and provides a composition for detecting an air leak at the time of the next lung surgery.

Item 1. A composition for detecting air leaks during lung surgery containing a surfactant.
Item 2. Item 2. The composition according to Item 1, wherein the surfactant comprises sophorose lipid.
Item 3. Item 2. The composition according to Item 1 or 2, further comprising a colorant.
Item 4. Item 6. The composition according to any one of Items 1 to 3, which is used in endoscopic surgery.

According to the composition for detecting air leakage of the present invention, in endoscopic surgery, it is not necessary to observe the inside of the thoracic cavity where the working space has disappeared during pressurization of the lung with a scope, and it is possible to more reliably confirm the presence or absence of air leakage. And it is possible to identify the location of the air leak.

Further, by including a colorant in the composition for detecting air leakage of the present invention, visibility can be improved.

Among the compositions for detecting air leaks of the present invention, those containing sophorose lipid have good elongation and retention on the lung surface, can be easily applied and removed, and have excellent foaming properties. ..

Hereinafter, the present invention will be described in detail.

It should be noted that, in the present specification, "comprise" also includes the meaning of "essentially consist of" and the meaning of "consist of".

The composition for detecting air leakage during lung surgery of the present invention is characterized by containing a surfactant.

As the surfactant, any of nonionic surfactant, cationic surfactant, amphoteric surfactant, and anionic surfactant can be used without particular limitation, and among them, it is not harmful to the human body and is not harmful to the human body. Those that can be used as pharmaceuticals, non-pharmaceutical products, cosmetics, foods, etc. are preferable.

Nonionic surfactants include, for example, polyoxyethylene (POE) -polyoxypropylene (POP) block copolymers (such as Poroxummer), POE-POP block copolymer adducts of ethylenediamine, POE sorbitan fatty acid esters, propylene glycol fatty acid esters. Kind, POE castor oil, POE alkylphenyl ether, POE alkyl ether, POE / POP alkyl ether, sorbitan fatty acid ester, sucrose fatty acid ester, alkyl polyglycoside, propylene glycol fatty acid ester, monostearate polyethylene glycol, glycerin fatty acid ester, soho Examples include loin lipid.

Examples of the amphoteric tenside include lecithin such as egg yolk lecithin and soybean lecithin, alkyldiaminoethylglycine or a salt thereof.

The cationic surfactant can be used without particular limitation, and examples thereof include benzethonium chloride and benzalkonium chloride.

The anionic surfactant can be used without particular limitation, and for example, polyoxyethylene alkyl sulfate, alkyl sulfate, alkylbenzene sulfonate, aliphatic α-sulfomethyl ester, α-olefin sulfonic acid and the like can be used. Can be mentioned.

Among the surfactants, biosurfactants with high safety are preferable, and sophorose lipid is particularly preferable. Sophorose lipids can be particularly suitably used for detecting air leaks during lung surgery, as shown in Examples described later. Sophorose lipid has good elongation and retention on the lung surface, can be easily applied and removed, and has excellent foaming property.

Sophorose lipid is generally a glycolipid composed of sophorose or sophorose having a partially acetylated hydroxyl group and a hydroxy fatty acid. The structure of the sophorose lipid is described in JP-A-2003-9896, JP-A-2016-160244 and the like. Sophorose is a sugar consisting of two molecules of glucose linked from β1 to 2. Hydroxy fatty acids are fatty acids having a hydroxyl group. Further, the sophorose lipid is roughly classified into an acid type in which the carboxyl group of the hydroxy fatty acid is liberated and a lactone type in which sophorose in the molecule is bound. Sophorose lipids obtained by fermentation of certain yeasts are usually a mixture of acid and lactone types and are obtained as an aggregate of more than 30 structural homologues.

As the sophorose lipid, for example, sophorolipid (registered trademark) (Salaya Co., Ltd.) exists as a commercially available product.

In the present invention, the surfactant can be used alone or in combination of two or more.

The content of the surfactant in the composition for detecting air leakage of the present invention is appropriately selected from the range of usually 0.001 to 100% by volume, preferably 0.01 to 75% by volume, and more preferably 0.1 to 50% by volume in the total amount of the composition. can do.

The composition for detecting an air leak of the present invention usually contains a solvent in addition to the surfactant, and examples of the solvent include water or a water-containing organic solvent containing water and an organic solvent. The organic solvent is preferably one that is freely miscible with water, and examples thereof include alcohols such as methanol and ethanol, ketones such as acetone, and organic acids such as acetic acid.

The composition for detecting air leakage of the present invention preferably contains a colorant. By including the colorant, the visibility is improved, and it becomes possible to confirm the presence or absence of an air leak and identify the location of the air leak more reliably.

The colorant (dye) is not particularly limited as long as the composition for detecting air leakage of the present invention can be colored, and any colorant can be used, and among them, it is not harmful to the human body, and is a pharmaceutical product, quasi-drug, cosmetic product, etc. Those that can be used as foods are preferable.

Examples of colorants include edible yellow Nos. 4 and 5, edible red Nos. 3 and 102, edible blue Nos. 1 and 2, edible green No. 3, yellow tricarbonate, red tricarbonate, and black iron oxide. Can be mentioned. As the colorant, blue and green colorants are preferable because they have excellent visibility.

The content of the colorant in the composition for detecting air leakage of the present invention is usually 0.00001 to 1w / v%, preferably 0.0001 to 0.1w / v%, and more preferably 0.001 to 0.01w / v% in the total amount of the composition. It can be appropriately selected from the range.

In addition to the surfactant, solvent and colorant, the composition for detecting air leakage of the present invention includes, if necessary, a suspending agent, a thickener, an antioxidant, a buffer, a pH adjuster, and a storage agent. Pharmaceutically acceptable ingredients such as agents and preservatives can be appropriately blended.

The pH of the composition for detecting an air leak of the present invention is usually pH 4 to 10, preferably pH 5 to 9.

The composition for detecting an air leak of the present invention may be in a concentrated form, and in that case, it can be appropriately diluted to an appropriate concentration at the time of use.

The composition for detecting air leaks of the present invention is applied to the surface of the lungs, and the lungs are pressurized and inflated. It is possible to confirm the presence or absence and identify the location of air leakage. Further, after confirming the presence or absence of air leakage, if necessary, the composition of the present invention is washed with physiological saline or the like to remove it.

The composition for detecting air leakage of the present invention is used in lung surgery, and the type of lung surgery is not particularly limited, and is suitable for surgery to remove a lung in which air leakage may occur from the remaining lung. Can be used. The composition for detecting air leakage of the present invention is particularly preferably used in endoscopic surgery. This is because in endoscopic surgery, when the lungs are pressurized, the working space disappears and it becomes difficult to observe the lung surface, but by using the composition of the present invention, the lungs are collapsed and then the inside of the thoracic cavity is scoped. This is because it is possible to confirm the presence or absence of an air leak and identify the location of the air leak by observing.

The method for applying the composition for detecting an air leak of the present invention to the lungs is not particularly limited, and a known method can be appropriately used.

The amount of the composition for detecting air leakage of the present invention to be applied can be appropriately determined according to various conditions such as the size of lungs.

The composition for detecting air leaks of the present invention is administered to mammals including humans.

The composition for detecting air leakage of the present invention does not require a scope to observe the inside of the thoracic cavity where the working space has disappeared during pressurization of the lung in endoscopic surgery, and more reliably confirms the presence or absence of air leakage and air. You will be able to identify the leak location.

As described above, by using the composition of the present invention, the presence or absence of air leakage can be confirmed more reliably, and it is expected that the risk of extension of hospitalization period, deterioration of patient's QOL, reoperation, etc. can be reduced. ..

Further, if the composition for detecting an air leak of the present invention contains a colorant, the visibility can be improved, and the presence or absence of an air leak can be confirmed and the location of the air leak can be identified more reliably.

Hereinafter, examples will be given to explain the present invention in more detail. However, the present invention is not limited to these examples and the like. In addition,% in this Example shall indicate w / v% unless otherwise specified.

Reference example 1: Creating a model of air leakage from the lungs using pig lungs
(1) A study was conducted using pig lungs purchased as animal organs for research. A tracheal tube with an inner diameter of 7.5 mm was inserted and fixed in the pig trachea, connected to a pressure bag, and the pig lung was pressurized and inflated. The pig lung was pressurized in water, and it was confirmed that there was no air leakage.

(2) The pig lung was taken out of the water, the surface of the lung was incised by a scalpel for 2 to 3 mm, and the pressure was applied again in the water, and it was confirmed that there was an air leak from the incision.

Test Example 1: Application of surfactant to lung surface and confirmation of foaming property
(1) Commercially available detergent containing sophorose lipid (Happy Elephant, Saraya Co., Ltd.), commercially available detergent not containing sophorose lipid (baby bottle vegetable washing, Pigeon Co., Ltd.), and lens fogging that can be used during surgery. The three anti-fog agents (Clarify and Covidien) were diluted with purified water to prepare a diluted detergent solution (1 time, 2 times, 5 times, 10 times, 20 times) as shown below.

The surfactants contained in Happy Elephant are alkyl ether sulfate sodium, alkyl polyglycoside and sophorose lipid, and the surfactants contained in baby bottle vegetable washing are polyoxyethylene sorbitan fatty acid ester and sucrose fatty acid. Esters and glycoceryl monocaprylate.

(2) The diluted surfactant was applied to the collapsed pig lung prepared in Reference Example 1 to pressurize the lung. After sufficient pressure was applied to inflate the lungs, the pressure was released and the lungs collapsed. At that time, the goodness of spreading on the lung surface at the time of application of each agent, the foaming property at the time of pressurization, and the retention of foam after collapse at the air leak site were evaluated.

(3) The same site was rinsed with 100 ml of purified water, and residual air bubbles were confirmed.

The coatability, foaming property, residual property and removability were evaluated according to the following criteria. The results are shown in Tables 2-4.
Applyability: Regarding the good spread of the solution on the lung surface, good was marked with ◯, slightly poor was marked with Δ, and poor was marked with ×.
Foaming property: Regarding the goodness of foaming, good was evaluated as ◯, slightly defective was evaluated as Δ, and defective was evaluated as ×.
Residuality: Regarding the retention of air bubbles after collapse, good was evaluated as ◯, slightly defective as Δ, defective as ×, and unevaluable as −.
Removability: Good was marked with ◯, slightly defective was marked with Δ, and defective was marked with × for the ease of removing air bubbles after rinsing.

Reference example 2: Confirmation of visibility at the time of application Of the pigments that can be used for all pharmaceutical products, quasi-drugs, and cosmetics, blue No. 1, green No. 3, and yellow No. 4, which are not considered to have strong dyeing properties, , And Yellow No. 5 were prepared as follows with 0.001% and 0.01% concentrations of dye aqueous solutions, which are the concentrations used in normal quasi-drug applications. Each dye was weighed in 0.01 g and dissolved in 100 ml of purified water to prepare a 0.01% aqueous dye solution. Moreover, this dye aqueous solution was diluted 10 times with purified water to prepare 0.001% dye aqueous solution. The prepared 0.001% and 0.01% dye aqueous solutions were applied to pig lungs, and the visibility was evaluated.

Visibility and removability were evaluated according to the following criteria. The results are shown in Tables 5 and 6.
Visibility: Good was marked with ○, slightly good was marked with Δ, and poor was marked with ×.
Pigment removal property: Those without pigmentation after removing the aqueous dye solution were marked with ◯, those with slight deposition were marked with Δ, and those with deposition and irremovable were marked with x.

Test Example 2: Confirmation of foaming property using a dye-containing surfactant Except for Clarify, which could not be evaluated in Test Example 1, visibility was obtained in Reference Example 2 for each dilution system of Happy Elephant and Baby Bottle Vegetable Wash. Except for the defective yellow No. 4 and yellow No. 5, blue No. 1 and green No. 3 were added at 0.001% and 0.01% concentrations, respectively, for coloring. Specifically, 0.01 g of each dye was weighed and dissolved in 10 ml of purified water to prepare a 0.1% aqueous dye solution. Using the dye aqueous solution, a dye-containing surfactant solution was prepared as follows. The same test as in Test Example 1 was carried out using the prepared 0.001% and 0.01% dye-containing surfactant solutions.

The coatability, foaming property, residual property, removability, visibility, and dye removability were evaluated according to the following criteria. The results are shown in Tables 9-16.
Applyability: Regarding the good spread of the solution on the lung surface, good was marked with ◯, slightly poor was marked with Δ, and poor was marked with ×.
Foaming property: Regarding the goodness of foaming, good was evaluated as ◯, slightly defective was evaluated as Δ, and defective was evaluated as ×.
Residuality: Regarding the retention of air bubbles after collapse, good was evaluated as ◯, slightly defective was evaluated as Δ, and defective was evaluated as ×.
Removability: Good was marked with ◯, slightly defective was marked with Δ, and defective was marked with × for the ease of removing air bubbles after rinsing.
Visibility: Good was marked with ○, slightly good was marked with Δ, and poor was marked with ×.
Pigment removal property: Those without pigmentation after removing the solution were marked with ◯, those with slight deposition were marked with Δ, and those with deposition and irremovable were marked with x.

Claims (4)

A composition for detecting air leakage during lung surgery, which contains a surfactant and is used by application. The composition according to claim 1, wherein the surfactant comprises sophorose lipid. The composition according to claim 1 or 2, further comprising a colorant. The composition according to any one of claims 1 to 3, which is used in endoscopic surgery.